Investigation of the effects of the toll-like receptor 4 pathway on immune checkpoint vista in pancreatic cancer

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dc.contributor.authorTopcu, Kubra Sena Bas
dc.contributor.authorKorucu, Emine Nedime
dc.contributor.authorMenevse, Esma
dc.contributor.authorKocak, Nadir
dc.contributor.authorDuran, Tugce
dc.date.accessioned2024-02-23T13:56:07Z
dc.date.available2024-02-23T13:56:07Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors of the pancreas. Preclinical studies show that it evades the immune system with immune checkpoints and promotes tumor development. V-domain Ig suppressor of T cell activation (VISTA) is a new immune-check point from the B7 family and is highly expressed in cancer cells. Overexpression of toll like receptor 4 (TLR4) in pancreatic adenocarcinoma is associated with induced tumorigenesis, tumor growth, resistancy to chemotherapy. Naloxone is an opioid and inhibits TLR4-ligand association. In this study, we investigated the relation of TLR4 and downstream pathways with immune-check point VISTA in pancreatic cancer proliferation. We initially collected pancreatic cancer-related datasets using the GEPIA2 and UALCAN databases. Based on this data obtained the effect of various concentrations and incubation times of naloxone were used on PANC-1 cells proliferation. A combination of naloxone and VISTA-siRNA were applied, and the effect of both naloxone and combined treatment on TLR4, Interleukin 1 receptor associated kinase 4 (IRAK4) and VISTA gene expression were analyzed in pancreatic cancer cells. As a result of analysis with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), gene expression levels of TLR4, IRAK4 and VISTA were significantly suppressed and cell proliferation was significantly reduced. We found that administration of naloxone and VISTA-siRNA in combination with PDAC cells suppressed signaling. Therefore, we considered that the relationship between VISTA and TLR4 signaling pathways and the other possible associated signal molecules may be an important marker in determining the response of immune checkpoint inhibitors in cancer treatment.en_US
dc.description.sponsorshipNecmettin Erbakan University Scientific Research Projects Coordination Unit [191315002]en_US
dc.description.sponsorshipThis study was funded by Necmettin Erbakan University Scientific Research Projects Coordination Unit, Project number 191315002.en_US
dc.identifier.doi10.1007/s10637-021-01209-z
dc.identifier.endpage528en_US
dc.identifier.issn0167-6997
dc.identifier.issn1573-0646
dc.identifier.issue3en_US
dc.identifier.pmid35113284en_US
dc.identifier.scopus2-s2.0-85124228958en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage519en_US
dc.identifier.urihttps://doi.org/10.1007/s10637-021-01209-z
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11070
dc.identifier.volume40en_US
dc.identifier.wosWOS:000750706100002en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofInvestigational New Drugsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectPancreatic Ductal Adenocarcinomaen_US
dc.subjectSirnaen_US
dc.subjectTlr4en_US
dc.subjectVistaen_US
dc.subjectImmunotherapyen_US
dc.titleInvestigation of the effects of the toll-like receptor 4 pathway on immune checkpoint vista in pancreatic canceren_US
dc.typeArticleen_US

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